肺癌同步放化療進(jìn)展.ppt

1、同步放化療在NSCLC的進(jìn)展,主要內(nèi)容,放療在早期NSCLC的進(jìn)展 同步放化療與靶向藥物治療NSCLC的進(jìn)展 同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展 同步放化療在晚期NSCLC的進(jìn)展,放療在早期NSCLC的進(jìn)展 同步放化療與靶向藥物治療NSCLC的進(jìn)展 同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展 同步放化療在晚期NSCLC的進(jìn)展,Stereotactic ablative radiotherapy (SABR) in potentially operable Stage I non-small cell lung cancer patients,立體定向消融放療治療潛在可手術(shù)的I期

2、非小細(xì)胞肺癌患者 Frank J. Lagerwaard Dept. of Radiation Oncology VUmc Cancer Center Amsterdam,I期NSCLC經(jīng)SABR治療后的局部控制情況,不選擇手術(shù)的原因,SABR對(duì)潛在科手術(shù)病人的基線特征,those with prior high-dose (chemo-)radiotherapy or pneumonectomy (N=23) GOLD Class 3 (N=216) WHO performance score 3 (N=23) 因共患心血管疾病排除手術(shù)的(N=94) 并發(fā)其他腫瘤的(N=50) 因主要共患病

3、除外手術(shù)的, e.g. 新發(fā)冠心病, 腎衰(N=68),SABR的治療劑量選擇,Performed at VUmc since April 2003 T1 tumors ( 3 cm), 腫瘤未達(dá)縱膈和胸壁 3 x 18 Gy 80%; 3 fx/week (BED 134 Gy) T1 tumors 達(dá)胸壁和縱膈, and T2 tumors 5 x 11 Gy 80%; 3 fx/week (BED 116 Gy) Tumors 臨近心包，臂叢神經(jīng)或肺門 8 x 7.5 Gy 80%; 3 fx/week (BED 105 Gy),SABR的主要 毒性,SABR治療117例潛在可手術(shù)患者的

4、結(jié)果,結(jié)論,應(yīng)用SABR是可行的 治療后30天死亡率為0%，對(duì)比該群患者術(shù)后死亡率為2.6% 盡管多數(shù)老年病人共患病率很高，經(jīng)SABR治療后中位生存仍超過5年 鼓勵(lì)內(nèi)鏡分期Nakajima T, 2010; Harley D, 2010 SABR數(shù)據(jù)支持隨機(jī)入組,放療在早期NSCLC的進(jìn)展 同步放化療與靶向藥物治療NSCLC的進(jìn)展 同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展 同步放化療在晚期NSCLC的進(jìn)展,LCCC 0511: Phase I/II Trial of Induction Carboplatin/Paclitaxel plus Bevacizumab followed by

5、 Concurrent Thoracic Conformal Radiotherapy with Carboplatin/Paclitaxel, Bevacizumab and Erlotinib in Stage IIIA/B NSCLC,卡鉑紫杉醇聯(lián)合貝伐單抗行誘導(dǎo)治療繼之以同步胸部適型放療聯(lián)合卡鉑紫杉醇，貝伐單抗和厄羅替尼治療IIIA/B期NSCLC的I/II期臨床研究 MA Socinski on behalf of the co-authors University of North Carolina, Yale University, Wake Forest University

6、and Northeast Medical Center,實(shí)驗(yàn)設(shè)計(jì),入組病人基線特征,Age (yrs), median (range) 61 (34-74) Sex (M:F) 23 (51%):18 (49%) Stage (IIIA:IIIB) 29 (64%):16 (36%) PS 0:1 26 (71%):13 (29% Histology Adeno 27 (60%) Squamous 12 (27%) Lg Cell 4 (9%) NSCLC NOS 2 (4%) Race Caucasian （高加索） 34 (78%) Black （黑人） 9 (20%) Asian 2

7、(4%) FEV1(), median (range) 2.4 (0.8-3.9),發(fā)生率多于等于1個(gè)病人且大于等于3級(jí)的毒性統(tǒng)計(jì),反應(yīng)率RECIST(n=45),Induction RR 39% (95% CI, 24-55%) ORR 60% (95% CI, 44-75%) *Judged 2-6 months after completion of RT,LCCC 生存結(jié)果,首要終點(diǎn)是PFS 假設(shè)檢驗(yàn)= PFS at 1 year = 50% 排除值if PFS 70%,LCCC高劑量同步放化療的相關(guān)臨床實(shí)驗(yàn),Socinski MA et al Cancer 92:1213-23, 2

8、001, Marks L et al J Clin Oncol 22:4329-40, 2004, Socinski MA et al J Clin Oncol 22:4341-50, 2004, Stinchcombe TE et al J Thorac Oncol 3:250-7, 2008, Socinski MA et al J Clin Oncol 26:2457-63, 2008, Socinski MA et al J Clin Oncol 27:389s, 2009,LCCC 0511-結(jié)論,誘導(dǎo)CbP + Bev 是可以耐受并有效的 同步Erlotinib + Bev 繼之以

9、強(qiáng)烈的同步放化療治療非鱗癌的NSCLC 的前提是 . 放療參數(shù)要預(yù)期設(shè)定 對(duì)食管炎行最佳支持治療 首要毒性是食管炎(經(jīng)常為遲發(fā)型) 聯(lián)合Erlotinib + Bevacizumab 不可行 This approach was associated with late PH in squamous histology patients PFS and OS 的結(jié)果相對(duì)于我們的歷史經(jīng)驗(yàn)不被看好 基于實(shí)驗(yàn)中觀察到得毒性加倍, 應(yīng)用Bev 和chemoRT 不被推薦,MultimodAlity treatment with Radio-chemoTherapy and Erlotinib in ad

10、vanced NSCLC (MARTE trial)進(jìn)展期NSCLC放化療聯(lián)合厄羅替尼的多模式治療（MARTE實(shí)驗(yàn)）,Sara Ramella Radiation Oncology Campus Bio-Medico University, Rome (Italy),材料和方法,之前經(jīng)過化療目前正在行放化療的病人 包括局限野放療(IF RT) 中值升高至59.4 Gy, 標(biāo)準(zhǔn)分割(1.8Gy/day) Erlotinib (E) 150 mg/day Chemotherapy: Gemcitabine (GEM) 300 mg/m2/week (E-GEM group) Pemetrexed

11、(PEM) 500mg/m2 every 3 weeks (E-PEM group),病人基線特征和治療相關(guān)毒性,病人基線特征和毒性統(tǒng)計(jì)數(shù)據(jù),有效性,隨訪范圍6-45 months 整體人群: 中位生存23.3 m PFS 4.7 m,27.9 vs 19.3 months; p=0.021,7.5 vs 3.7 months; p=0.05,27.9 vs 18.2 months; p=0.004,23.1 vs 22 months; p=0.791,非鱗癌總生存,鱗癌總生存,結(jié)論,臨床前期數(shù)據(jù)證實(shí)厄羅替尼的靶向治療有放射增敏作用 之前經(jīng)過多次化療的病人行厄羅替尼聯(lián)合同步放化療治療是可行的有

12、效的 臨床生物學(xué)標(biāo)志物保障了放射治療的效應(yīng),Determination of standard dose cetuximab together with concurrent individualised, isotoxic accelerated radiotherapy and cisplatin-vinorelbine for patients with stage III non-small cell lung cancer: A phase I study(NCT00522886),測(cè)定標(biāo)放療準(zhǔn)計(jì)量的西妥昔單抗聯(lián)合同步個(gè)體化，同毒性加速放療聯(lián)合順鉑長(zhǎng)春瑞賓治療III期非小細(xì)胞肺癌的I

13、期臨床研究 Anne-Marie C. Dingemans Gerben Bootsma Angela van Baardwijk Bart Reijmen Rinus Wanders Monique Hochstenbag Arne van Belle Ruud Houben Philippe Lambin Dirk de Ruysscher,治療流程表,*Vinorelbine: step 1 10 mg/m2d 1-8, 8 mg/m2 d22-29 step 2 20 mg/m2d 1-8, 8 mg/m2 d22-29 step3 20 mg/m2d 1-8, 15 mg/m2 d

14、22-29,毒性,治療3個(gè)月后經(jīng)FDG-PET測(cè)定代謝反應(yīng) (N=22) CR:8 PR:11 PD:3 結(jié)論 同步放化療聯(lián)合順鉑，長(zhǎng)春瑞賓及西妥昔單抗時(shí)可行的 長(zhǎng)春瑞賓不能選擇最大劑量 毒性在預(yù)期內(nèi) 3月后治療結(jié)果令人鼓舞,放療在早期NSCLC的進(jìn)展 同步放化療與靶向藥物治療NSCLC的進(jìn)展 同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展 同步放化療在晚期NSCLC的進(jìn)展,力比泰卡鉑同步3D適形放療后以力比泰卡鉑鞏固化療治療中國(guó)局部晚期NSCLC患者,Ma S, et al. ASCO 2009 abstract e18502.,摘要e18502：研究設(shè)計(jì),摘要e18502：研究結(jié)果 緩解情

15、況,摘要e18502：研究結(jié)果 不良反應(yīng),放療在早期NSCLC的進(jìn)展 同步放化療與靶向藥物治療NSCLC的進(jìn)展 同步放化療聯(lián)合培美曲塞治療NSCLC的研究進(jìn)展 同步放化療在晚期NSCLC的進(jìn)展,15-year (very) long-term survival (VLTS) and competing risks (CR) analysis of induction (IND) chemotherapy (CTx) with three cycles cisplatin(P)/etoposide(E) followed by concurrent (cc) chemoradiation (CT

16、x/RTx) PE/45 Gy (1.5 Gy bid) plus surgery (S) = TRIMODALITY phase-II West German Cancer Centre (WGCC) trial (JCO 98).R.Hepp1, T.C.Gauler2, C. Poettgen1, S. Korfee2, S. Bildat2, G. Stamatis3, S. Seeber4, H. Wilke4, V. Budach5, M. Stuschke1, W. E. E. Eberhardt2,西德癌癥中心TRIMODALITY II期臨床試驗(yàn)：三周期EP誘導(dǎo)化療繼以同步放

17、化療聯(lián)合手術(shù)治療的一項(xiàng)15年長(zhǎng)期生存和競(jìng)爭(zhēng)風(fēng)險(xiǎn)分析,試驗(yàn)設(shè)計(jì),OS (stage), OS (R0) and OS (R0: pCR vs no pCR),Fig. 2. OS (stage),Fig. 3. OS (R0),Fig. 4. OS (R0: pCR),LTS/VLTS 在選擇性亞群的CR分析,Tab.1. VLTS in selected subgroups,Fig.5. Competing Risk-analysis,結(jié)論,LTS/VLTSontheWGCC-trialJCO98定義為第一個(gè)選擇性可切除IIIA期NSCLC患者的隨機(jī)對(duì)照多中心臨床試驗(yàn) 探索性分析顯示前期治療對(duì)

18、15年長(zhǎng)期結(jié)果無影響 基于選擇性的R0-可切除的IIIA和IIIB期患者繼以誘導(dǎo)治療手長(zhǎng)期隨訪結(jié)果優(yōu) 60個(gè)月的競(jìng)爭(zhēng)性風(fēng)險(xiǎn)分析提示(心血管，肺疾病，再發(fā)肺癌和再發(fā)腫瘤是香港風(fēng)險(xiǎn) (5yrs),SOCCAR trial results:,Comparing toxicity and efficacy of hypofractionated concurrent,chemoradiation to published regimens,Cancer Research UK advisory boards: Eli Lilly McMenamin,R: speakers honoraria: Pfi

19、zer; advisory boards: Bayer, GSK; support for meetings: GSK, Ibt, Ferring, Boeringer,Snee, M:,nil,Cancer Research UK & UCL Cancer Trials Centre Trial funding and Disclosure,3,CONCURRENT ARM 55Gy/20f/4weeks cisplatinum 80mg/m2 weeks 1,4 vinorelbine 15mgs/m2 weekly 4 weeks cisplatinum 80mg/m2 day 1 vi

20、norelbine 25mg/m2 d 1, d 8 2 cycles,SEQUENTIAL ARM cisplatinum 80mg/m2 day 1 vinorelbine 25mg/m2 day 1, 8 4 cycles 4 weeks 55Gy/20f/4weeks,SOCCAR,Trial Design 病理學(xué)確診 NSCLC stage III , PS 0-1, CT mediastinoscopy, PET-CT unsuitable for surgery,SOCCAR,NSCLC Stage III PS 0 - 1,CON,SEQ,n median 1 year 2 y

21、ear 3 year 5 year Local PD,67 27.4 m 73.1% 54% 38% 33.6% 10%,59 18.6 m 83.1% 42% 27% NR 22%,Con Seq Months,Cancer Research UK & UCL Cancer Trials Centre Concurrent Schedules Compared,Trial,no.,%2ys,RT,CT,%TRM,G3/4oes,patients,Gy/f,SOCCAR 2010,70,54,55/20,cis/vin,4,17%,Jeremic 1996,65,43,69.6/58/6w c

22、arbo/etop,0,8,Belderbos 2006 Fournel 2005 Curran 2003 Huber 2006 Furuse 1999 Zatloukal 2004 Belani 2005 Vokes 2004,66 100 201 99 156 51 92 182,39 39 37 36 34.6 34 31 29,66/24 66/33 60/30 60/30 56/28split 60/30 63/34 66/33,daily cis cis/etop cis/vbl wkly taxol cis/vind cis/vin carbo/tax carbo/tax,1.5

23、 10 3 0 0.6 0 2 ?,17 32 25 13 3 18 28 31,Conclusions,Cancer Research UK & UCL Cancer Trials Centre, 55Gy/20f/26-28d 同步順鉑聯(lián)合長(zhǎng)春瑞賓治療III NSCLC, PS 0-1高度有效, 2 year survival 同步放化療組 50%, 相比于16 RCTs, 1733 患者經(jīng)同步CTRT治療后的 總生存最高且耐受性良好,Randomized phase II trial of uracil/tegafur (UFT) and cisplatin versus vinorel

24、bine and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III,non-small-cell lung cancer,NJLCG 0601,試驗(yàn)?zāi)繕?biāo),尿嘧啶替加氟(UFT)聯(lián)合順鉑(UP arm)對(duì)比長(zhǎng)春瑞賓聯(lián)合順鉑輔以同步胸部放療,治療進(jìn)展期不可切除的stage III NSCLC 的有效性和安全性., 首要終點(diǎn),整體有效率(ORR), 次要終點(diǎn),Progression free survival (PFS) Overall survival (OS) Toxicity profile,RANDOMIZATION Stratified factor,Age Gender Histology Stage,59 /6064/6569/7075 Male/Female Adeno./Sq./Large/Others IIIA/IIIB,ENROLLMENT,(n=70),UP arm (n=36) (35 patients were evaluable) UFT : 400mg/m2, day 1-14, 29-42